Glioblastoma multiforme (GBM) is characterized by diffuse infiltration of the brain, active regional recurrence, low cure proportion, and limited chemotherapy efficiency. MutS homolog 6 (MSH6) is a component of the mismatch repair system related to the oncogenesis, tumor evolution, and recurrence of GBM. The impact of MSH6 upregulation on the tumor microenvironment (TME) of GBM and the feasibility of MSH6 as a potential target to improve the prognosis remain unknown. The expression of MSH6 at mRNA level indicated that MSH6 expressed higher in GBM tissues than that in normal ones. The transwell assay and expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) suggested that the capability of invasion and migration in U251-MSH6 was more stubborn. The intracranial tumor model was established with nude mice to further explore in vivo. The time-weight curve, overall survival, tumor volumes, expression levels of MMP-2 and MMP-9 in tissue, and hematoxylin and eosin staining all indicated that MSH6 had a positive effect on metastasis. The expression levels of related proteins suggested that the hypoxia TME induced by MSH6 may promote metastasis via epithelial to mesenchymal transition, stemness, and angiogenesis progress. MSH6 is an overexpressed oncogene in human GBM tissues, which accelerated metastasis by regulating hypoxia inducible factor-1A (HIF1A) to form a hypoxic TME in GBM. The MSH6 was a vital marker of GBM, making it a promising therapeutic target.

中文翻译：

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MSH6通过调节HIF1A促进多形性胶质母细胞瘤的转移，加重了缺氧的微环境

多形性胶质母细胞瘤（GBM）的特征在于大脑弥漫性浸润，活跃的区域复发，治愈率低和化疗效率有限。MutS同系物6（MSH6）是错配修复系统的组成部分，与GBM的发生，肿瘤演变和复发有关。的影响MSH6上调上GBM的肿瘤微环境（TME）和的可行性MSH6作为改善预后的潜在目标仍然是未知的。的表达MSH6在mRNA水平表明，MSH6GBM组织中的表达高于正常组织。Transwell分析和基质金属蛋白酶2（MMP-2）和基质金属蛋白酶9（MMP-9）的表达水平表明，U251-MSH6的侵袭和迁移能力更加顽固。用裸鼠建立了颅内肿瘤模型以进一步探索体内。时间-重量曲线，总生存期，肿瘤体积，组织中MMP-2和MMP-9的表达水平以及苏木精和曙红染色均表明MSH6对转移具有积极作用。相关蛋白的表达水平表明，MSH6诱导的缺氧TME可能通过上皮向间充质转变，干性和血管生成进程促进转移。MSH6是在人GBM组织中过表达的癌基因，它通过调节缺氧诱导因子1A（HIF1A）加速转移，从而在GBM中形成低氧TME。该MSH6是GBM的一个重要标志，使其成为一个有前途的治疗靶点。